Chondroitin Sulfate Protects SH-SY5Y Cells from Oxidative Stress by Inducing Heme Oxygenase-1 via Phosphatidylinositol 3-Kinase/Akt

Cañas, Noelia; Valero, Teresa; Villarroya, Mércedes; Montell, E.; Vergés, Josep; Garcı́a, Antonio G.; López, Manuela G.

doi:10.1124/jpet.107.123505

Cited by 85 publications

(70 citation statements)

References 41 publications

(40 reference statements)

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“…Chondroitin sulfate has further been shown to decrease the production of ROS generated by H 2 O 2 or mitochondrial disruption by induction of the antioxidant enzyme heme oxygenase-1 through the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway (45). Thus, intact PNNs could serve as a protective shield to neutralize ROS either directly and/or via activation of intracellular pathways to boost the cellular antioxidant capacity.…”

Section: Discussionmentioning

confidence: 99%

“…Through their poly-anionic nature, PNNs chelate iron (43), thereby limiting the formation of iron-generated reactive hydrogen radicals. Components of the PNNs, such as hyaluronan and chondroitin sulfate, have antioxidant properties (44,45) and can reduce the generation of hydroxyl radical (OH_) via their capacity to chelate transition metals and limit the initiation of Harber-Weiss and Fenton's reactions. This, in turn, decreases lipid peroxidation, DNA damage, and protein oxidation.…”

Section: Discussionmentioning

confidence: 99%

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Perineuronal nets protect fast-spiking interneurons against oxidative stress

Cabungcal

Steullet

Morishita

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

419

381

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A hallmark of schizophrenia pathophysiology is the dysfunction of cortical inhibitory GABA neurons expressing parvalbumin, which are essential for coordinating neuronal synchrony during various sensory and cognitive tasks. The high metabolic requirements of these fast-spiking cells may render them susceptible to redox dysregulation and oxidative stress. Using mice carrying a genetic redox imbalance, we demonstrate that extracellular perineuronal nets, which constitute a specialized polyanionic matrix enwrapping most of these interneurons as they mature, play a critical role in the protection against oxidative stress. These nets limit the effect of genetically impaired antioxidant systems and/or excessive reactive oxygen species produced by severe environmental insults. We observe an inverse relationship between the robustness of the perineuronal nets around parvalbumin cells and the degree of intracellular oxidative stress they display. Enzymatic degradation of the perineuronal nets renders mature parvalbumin cells and fast rhythmic neuronal synchrony more susceptible to oxidative stress. In parallel, parvalbumin cells enwrapped with mature perineuronal nets are better protected than immature parvalbumin cells surrounded by less-condensed perineuronal nets. Although the perineuronal nets act as a protective shield, they are also themselves sensitive to excess oxidative stress. The protection might therefore reflect a balance between the oxidative burden on perineuronal net degradation and the capacity of the system to maintain the nets. Abnormal perineuronal nets, as observed in the postmortem patient brain, may thus underlie the vulnerability and functional impairment of pivotal inhibitory circuits in schizophrenia.critical period | extracellular matrix | glutamate cysteine ligase | glutathione | neuronal synchronization F ast-spiking interneurons expressing parvalbumin (PV) constitute a subpopulation of GABA cells that control the output of principal neurons and are necessary for fast rhythmic neuronal synchrony, facilitating information processing during cognitive tasks (1, 2). To coordinate the activity of neuronal assemblies, PV cells are interconnected by both chemical and electrical synapses, have the capacity to fire at high frequency without adaptation, and selectively position inhibitory synaptic terminals onto the cell body and axon initial segment of their target neurons. Fast-spiking properties consequently impose high metabolic demand and increased mitochondrial density, which renders PV cells, but not other interneurons such as calretinin and calbindin cells, particularly sensitive to oxidative stress (3). For instance, ketamine induces superoxide overproduction that strongly impairs PV cells (i.e., loss of normal phenotype including PV immunoreactivity but without cell death) (4, 5). Moreover, severe environmental stressors produce oxidative stress in the brain and impair PV cells (6)(7)(8). Postmortem studies reveal PV-cell anomalies in individuals with schizophrenia or bipolar disorder (9-11). ...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Perineuronal nets protect fast-spiking interneurons against oxidative stress

Cabungcal

Steullet

Morishita

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

419

381

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“…42,43) In addition, it was reported to reduce cell damage by scavenging free radicals, inhibiting the activation of apoptosis, and eliciting an anti-inflammatory effect at the synovial membrane and chondrocyte level. 26,44,45) These cytoprotective actions of CS may reduce the toxicity of PAMAM dendrimers.…”

Section: Fig 7 In Vivo Gene Expression Of Each Complex Administeredmentioning

confidence: 99%

Ternary Complex of Plasmid DNA Electrostatically Assembled with Polyamidoamine Dendrimer and Chondroitin Sulfate for Effective and Secure Gene Delivery

Imamura

Kodama

Higuchi

et al. 2014

Biological & Pharmaceutical Bulletin

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The purpose of this study was to develop a ternary complex of plasmid DNA (pDNA) electrostatically assembled with polyamidoamine (PAMAM) dendrimer and chondroitin sulfate (CS) for effective and secure gene delivery. PAMAM dendrimers are new cationic polymers that are expected to be used as gene delivery vectors. However, cationic non-viral gene vectors showed cytotoxicity by binding to negative cellular membranes. We therefore prepared a ternary complex by adding CS, an anionic polymer, and examined its usefulness. The pDNA/PAMAM dendrimer complex (PAMAM dendriplex) and the PAMAM dendriplex coated by CS (CS complex) showed nanoparticles with positive ζ-potential and negative ζ-potential, respectively. The CS complex had no cytotoxicity against B16-F10 cells and no agglutination activity, although severe cytotoxicity and high agglutination were observed in the PAMAM dendriplex. As a result of an in vitro gene expression study of B16-F10 cells, not only the PAMAM dendriplex but also the CS complex showed high transfection efficiency. The transfection efficiency of the CS complex was significantly inhibited by clathrinmediated endocytosis inhibitor (chlorpromazine), caveolae-mediated endocytosis inhibitor (genistein), and hypothermia. Tail-vein injection of the CS complex into mice led to significantly higher gene expression in the spleen than the PAMAM dendriplex. Thus, the ternary complex of pDNA electrostatically assembled with PAMAM denriplex and CS showed safe high gene expression in the spleen. This vector is expected to be useful for useful gene delivery.Key words ternary complex; chondroitin sulfate; polyamidoamine dendrimer; gene delivery Gene therapy is expected to be an effective method to treat cancer, infection, innate immunodeficiency and cardiovascular diseases.1-4) The success of gene therapy is largely dependent on the development of vectors capable of effectively delivering foreign genes into targeted cells. One major approach in gene therapy is based on cationic polymers, such as polyethylenimine (PEI), polylysine, polyarginine, and chitosan.5-8) When cationic polymer-encapsulated plasmid DNA (pDNA) makes association with the cell surface, it enters the cells by endocytosis.Polyamidoamine (PAMAM) dendrimers are new cationic polymers, which are highly branched radial polymers that have specific and systematically variable size, shape and chemical structure. Their radical structure contains a 2-carbon ethylenediamine core and primary amino groups on the surface. Successive generations (G) have increasing diameter and double the surface functional amino groups of the preceding generation.9,10) PAMAM dendrimers can be used as carriers for pDNA and show high transfection efficiency. 11,12)The pDNA/PAMAM dendrimer complexes (PAMAM dendriplex) are formed by electrostatic interactions and initiate cell entry through binding to anionic phospholipids on the cell membrane. With increasing generations of dendrimers, the PAMAM dendriplex showed higher transfection efficiency, which depended on the charge rati...

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“…In contrast, chondroitin sulfate has been shown to protect human neuroblastoma SH-SY5Y cells against H 2 O 2 -induced oxidative stress [99], as well as rat hippocampal slices against oxygen and glucose deprivation toxicity [100]. This discrepancy may be explained by the different experimental models and the extremely high concentrations of chondroitin sulfate used in the latter studies (0.1 and 0.3 mM).…”

Section: Cardiocytoprotective Effect Of Biglycancontrasting

confidence: 44%

Novel approaches of pharmacological preconditioning: the role of biglycan and miRNAs

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Chondroitin Sulfate Protects SH-SY5Y Cells from Oxidative Stress by Inducing Heme Oxygenase-1 via Phosphatidylinositol 3-Kinase/Akt

Cited by 85 publications

References 41 publications

Perineuronal nets protect fast-spiking interneurons against oxidative stress

Perineuronal nets protect fast-spiking interneurons against oxidative stress

Ternary Complex of Plasmid DNA Electrostatically Assembled with Polyamidoamine Dendrimer and Chondroitin Sulfate for Effective and Secure Gene Delivery

Novel approaches of pharmacological preconditioning: the role of biglycan and miRNAs

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